Ahead of Print -Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels - Volume 20, Number 12—December 2014 - Emerging Infectious Disease journal - CDC

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Ahead of Print -Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels - Volume 20, Number 12—December 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 12—December 2014

Research

Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels

On This Page

• Materials and Methods
• Results
• Discussion
• Suggested Citation

Figures

• Figure 1
• Figure 2
• Figure 3
• Figure 4
• Figure 5

Tables

• Table 1

Danielle R. Adney, Neeltje van Doremalen, Vienna R. Brown, Trenton Bushmaker, Dana Scott, Emmie de Wit, Richard A. Bowen1 , and Vincent J. Munster1

Author affiliations: Colorado State University, Fort Collins, Colorado, USA; (D.R. Adney, V.R. Brown, R.A. Bowen);National Institutes of Health, Hamilton, Montana, USA (N. van Doremalen, T. Bushmaker, D. Scott, E. de Wit, V.J. Munster)

Suggested citation for this article

Abstract

In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission.

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 related to a fatal human case of pneumonia in Saudi Arabia (1). Currently, >800 cases of MERS have been identified, and the estimated case-fatality rate is ≈35% (2). Most cases have been identified on the Arabian Peninsula, but several travel-associated cases have been reported (2–4). Human-to-human transmission has been reported, predominantly among persons in health care facilities and households; the rate of human infection by zoonotic transmission from a reservoir source is currently not known (4–6).

The close phylogenetic relationship of human MERS-CoV isolates with those obtained from bats initially suggested a direct link between the emergence of MERS-CoV and a putative natural reservoir (7–9). Anecdotal reports mentioned contact of MERS-CoV–infected patients with camels and goats, suggesting that livestock might be the intermediate reservoir host for MERS-CoV (4,10–12). Serologic studies revealed widespread prevalence of MERS-CoV–specific antibodies in dromedary camels from several countries that reported MERS cases (4,13–19). Further, MERS-CoV RNA was detected in nasal swab samples obtained from 3 camels on a farm linked to 2 human MERS-CoV cases, and the virus was isolated from nasal swab samples from dromedary camels in Qatar (14). MERS-CoV isolation and subsequent full genome sequencing directly linked a dromedary camel and a fatal MERS-CoV case in a person in Saudi Arabia (20,21). Despite these associations, the role of camels as a primary reservoir for MERS-CoV is still debated (22,23). Here we report on the experimental inoculation of 3 camels with a human isolate of MERS-CoV.

Ms. Adney is a graduate student at Colorado State University in Fort Collins, Colorado. Her research focus is on the pathogenesis of emerging infectious diseases.

Acknowledgments

We thank Bart Haagmans and Ron Fouchier, for providing MERS-CoV (isolate hCoV-EMC/2012); Tina Thomas, Dan Long, and Rebecca Rosenke for histopathologic examination; and Anita Mora and Ryan Kissinger for figure preparation.

This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Animal Models Core at Colorado State University. D.R.A. was supported through the Infectious Disease: Translational Research Training Program at Colorado State University.

All animal work in this study was approved by the Institutional Animal Care and Use Committee of Colorado State University and was performed in compliance with recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institute of Health.

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Figures

• Figure 1. Clinical signs in dromedary camels inoculated with Middle East respiratory syndrome coronavirus (MERS-CoV). A) Nasal discharge observed in camel 3; each of 3 inoculated camels had nasal discharge during...
• Figure 2. Virus shedding from the upper respiratory tract in dromedary camels inoculated Middle East respiratory syndrome coronavirus MERS-CoV (MERS-CoV). Shedding was determined by A) infectious titers by plaque assay and...
• Figure 3. Virus shedding determined by oral swabs obtained from dromedary camels inoculated with Middle East respiratory syndrome coronavirus MERS-CoV (MERS-CoV. Shedding was determined by A) determining infectious titers and B)...
• Figure 4. Virus titers in tissues collected from dromedary camel 1 inoculated with MERS-CoV. Tissues were collected at 5 days postinoculation (dpi) for camel 1, 28 dpi for vamel 2 and...
• Figure 5. Histopathologic changes at 5 days postinoculation in camel 1 inoculated with MERS-CoV. Tissues were collected and stained with hematoxylin and eosin (top row). Anti-MERS-CoV immunohistochemical results (bottom row) are...

Table

• Table 1. Antibody titers against MERS-CoV in dromedary camels inoculated with the virus as determined by 90% plaque reduction assay

Suggested citation for this article: Adney DR, van Doremalen N, Brown VR, Bushmaker T, Scott D, de Wit E, et al. Replication and shedding of MERS-CoV in upper respiratory tract of inoculated dromedary camels. Emerg Infect Dis. 2014 Dec [date cited]. http://dx.doi.org/10.3201/eid2012.141280

DOI: 10.3201/eid2012.141280

1These senior authors contributed equally to this article.